电离辐射对小鼠骨髓造血干/祖细胞中CD47表达的影响

doi:10.13481/j.1671-587x.20200610

Abstract

Abstract: Objective

To investigate the damage of bone marrow hematopoietic stem/progenitor cells （HSCs/HPCs） and the changes of CD47 expression levels in the HSCs/HPCs of the mice after X-ray irradiation，and to clarify the role of CD47 in irradiation-induced injury of HSCs/HPCs.

Methods

The C57BL/6 mice were divided into nonirradation group and irradation group， and the C57BL/6 mice in irradation group were divided into 18 h， 5 d， 11 d， and 6 weeks after irradiation subgroups，and there were 5 mice in each group. The mice in irradation groups were given by an X-ray irradiator with a dose of 3.0 or 9.0 Gy at one time. The mice were sacrificed at different time points after irradiation.The percentages of HSCs to HPCs in bone marrow of the mice in various groups were detected by flow cytometry， and the expression levels of CD47 in HSCs/HPCs of the mice in various groups were detected at different time points after irradiation.

Results

The level of CD47 expression in HPCs of the mice in non-irradation group was more than 2-fold higher than the mature HSCs in bone marrow （P<0.05）. Compared with non-irradation group， there were no statistical differences in the CD47 expression levels in HPCs of the mice in irradation groups at 18 h， 5 d， and 11 d after irradation （P>0.05）； the percentages of HPCs in lineage-negative （lin^－） cells and whole bone marrow cells were decreased significantly（P<0.05）， which returned to normal level at 6 weeks after irradiation. Compared with non-irradiation group， the CD47 expression level in HSCs of the mice in 18 h after irradiation group was increased （P<0.01）， and there were no significant differences in the CD47 expression levels in HSCs of the mice in 5 d，11 d and 6 weeks after irradiation groups（P>0.05）； the percentage of HSCs in Lin^－ cells in 18 h after irradiation group was increased （P<0.01）， and the percentage of HSCs cells in whole bone marrow cells in 11 d after irradiation group was decreased （P<0.01）.The percentage of CD47 low expression subgroup was significantly lower than that of CD47 high expression subgroup in the HPCs in 18 h after irradiation group（P<0.01）.The percentage of CD47 low expression subgroup in the HPCs in 5 d，11 d and 6 weeks after irradiation groups were similar to those in CD47 high expression subgroup.

Conclusion

The total body ionizing radiation can cause the bone marrow damage in the mice and the decreasing in the percentage of HSCs to HPCs， and the mechanism may be related to the transient increase of CD47 expression in the HSCs after irradiation.

Key words: ionizing radiation, myelosuppression, hematopoietic stem cells, hematopoietic progenitor cells, CD47

CLC Number:

R144.1

Guangyao XIE,Feng WANG,Ting ZHANG,Yanhou LIU,Yongguang YANG. Effect of ionizing irradiation on expression of CD47 in bone marrow hematopoietic stem/progenitor cells in mice[J].Journal of Jilin University(Medicine Edition), 2020, 46(6): 1169-1176.

Figures/Tables 8

Fig. 1

Fig. 2

Fig. 4

Fig. 5

Fig. 6

Fig. 7

Fig.8

Fig.9

References 24

1	HUR W， YOON S K. Molecular Pathogenesis of radiation-induced cell toxicity in stem cells.［J］ Int J Mol Sci， 2017， 18（12）： 2749.
2	SQUILLARO T， GALANO G， DE ROSA R， et al. Concise review： the effect of low-dose ionizing radiation on stem cell biology： a contribution to radiation risk［J］. Stem Cells， 2018， 36（8）： 1146-1153.
3	SHAO L， FENG W， LI H， et al. Total body irradiation causes long-term mouse BM injury via induction of HSC premature senescence in an Ink4a- and Arf-independent manner ［J］. Blood， 2014， 123（20）： 3105-3115.
4	WANG Y， SCHULTE B A， LARUE A C， et al. Total body irradiation selectively induces murine hematopoietic stem cell senescence ［J］. Blood， 2006， 107（1）： 358-366.
5	OLDENBORG P A， ZHELEZNYAK A， FANG Y F， et al. Role of CD47 as a marker of self on red blood cells ［J］. Science， 2000， 288（5473）： 2051-2054.
6	JAISWAL S， JAMIESON C H M， PANG W W， et al. CD47 is upregulated on circulating hematopoietic stem cells and leukemia cells to avoid phagocytosis ［J］. Cell， 2009， 138（2）： 271-285.
7	BURGER P， HILARIUS-STOKMAN P， DE KORTE D， et al. CD47 functions as a molecular switch for erythrocyte phagocytosis ［J］. Blood， 2012， 119（23）： 5512-5521.
8	CHEN M， WANG Y， WANG H， et al. Elimination of donor CD47 protects against vascularized allograft rejection in mice ［J］. Xenotransplantation， 2018： e12459.
9	ISENBERG J S， HYODO F， MATSUMOTO K， et al. Thrombospondin-1 limits ischemic tissue survival by inhibiting nitric oxide-mediated vascular smooth muscle relaxation ［J］. Blood， 2007， 109（5）： 1945-1952.
10	SAGAWA M， SHIMIZU T， FUKUSHIMA N， et al. A new disulfide-linked dimer of a single-chain antibody fragment against human CD47 induces apoptosis in lymphoid malignant cells via the hypoxia inducible factor-1alpha pathway ［J］.Cancer Sci， 2011， 102（6）： 1208-1215.
11	ISENBERG J S， MAXHIMER J B， HYODO F， et al. Thrombospondin-1 and CD47 limit cell and tissue survival of radiation injury ［J］. Am J Pathol， 2008， 173（4）： 1100-1112.
12	MAXHIMER J B， SOTO-PANTOJA D R， RIDNOUR L A， et al. Radioprotection in normal tissue and delayed tumor growth by blockade of cd47 signaling ［J］. Sci Transl Med， 2009， 1（3）： 3-7.
13	SOTO-PANTOJA D R， RIDNOUR L A， WINK D A， et al. Blockade of CD47 increases survival of mice exposed to lethal total body irradiation ［J］. Sci Rep， 2013， 3： 1038.
14	WASELENKO J K， MACVITTIE T J， BLAKELY W F， et al. Medical management of the acute radiation syndrome： recommendations of the Strategic National Stockpile Radiation Working Group ［J］. Ann Intern Med， 2004， 140（12）： 1037-1051.
15	SHAO L， LUO Y， and ZHOU D. Hematopoietic stem cell injury induced by ionizing radiation ［J］. Antioxid Redox Signal， 2014， 20（9）： 1447-1462.
16	CHANG V Y， TERMINI C M， and CHUTE J P. Young endothelial cells revive aging blood ［J］. J Clin Invest， 2017， 127（11）： 3921-3922.
17	RODRIGUES-MOREIRA S， MORENO S G， GHINATTI G， et al. Low-dose irradiation promotes persistent oxidative stress and decreases self-renewal in hematopoietic stem cells ［J］. Cell Rep， 2017， 20（13）： 3199-3211.
18	KURIYAMA T， TAKENAKA K， KOHNO K， et al. Engulfment of hematopoietic stem cells caused by down-regulation of CD47 is critical in the pathogenesis of hemophagocytic lymphohistiocytosis ［J］. Blood， 2012， 120（19）： 4058-4067.
19	CHHABRA A， RING A M， WEISKOPF K， et al. Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy ［J］. Sci Transl Med， 2016， 8（351）： 351.
20	GEORGE B M， KAO K S， KWON H S， et al. Antibody conditioning enables mhc-mismatched hematopoietic stem cell transplants and organ graft tolerance ［J］. Cell Stem Cell， 2019， 25（2）： 185-192.
21	MILLER T W， SOTO-PANTOJA D R， SCHWARTZ A L， et al. CD47 receptor globally regulates metabolic pathways that control resistance to ionizing radiation ［J］. J Biol Chem， 2015， 290（41）： 24858-24874.
22	STIRLING E R， COOK K L， ROBERTS D D， et al. Metabolomic analysis reveals unique biochemical signatures associated with protection from radiation induced lung injury by lack of cd47 receptor gene expression ［J］. Metabolites， 2019， 9（10）： 218.
23	GAO Q， CHEN K， GAO L， et al. Thrombospondin-1 signaling through CD47 inhibits cell cycle progression and induces senescence in endothelial cells ［J］. Cell Death Dis， 2016， 7（9）： e2368.
24	KAUR S， SOTO-PANTOJA D R， STEIN E V， et al. Thrombospondin-1 signaling through CD47 inhibits self-renewal by regulating c-Myc and other stem cell transcription factors ［J］. Sci Rep， 2013， 3： 1673.

[1]	Hongyuan TIAN,Caiyun YIN,Li WANG,Peiyun HU,Chenyang ZHANG,Qiuyue LI,Qingzhao ZHENG,Yali QI,Fang FANG,Zhicheng WANG. Effects of hydroxyurea combined with radiation on cell cycle and apoptosis of cells after silencing ATRX [J]. Journal of Jilin University(Medicine Edition), 2023, 49(3): 590-598.
[2]	TANG Geng, SHI Yaoting, KONG Weixuan, KE Xiyang, LI Chengxiang, QIU Yuqi, YU Lei, YANG Yanming, WANG Zhicheng. Effect of ionizing radiation on DNA damage repair in HeLa cells silencing ATRX [J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 981-985.
[3]	REN Ming, ZHANG Yan, LI Ronghang, LI Qiuju. Effect of Ginkgo biloba L. extract on oxidative stress and activity of protein kinase C in spleen tissue of mice with irradiation damage [J]. Journal of Jilin University(Medicine Edition), 2019, 45(02): 223-227.
[4]	QUAN Xiaoyue, LIU Bailong, LIU Min, DONG Lihua. Treatment of lung squamous cell carcinoma with apatinib in patient who couldn't tolerate chemotherapy: A case report and literature review [J]. Journal of Jilin University Medicine Edition, 2018, 44(03): 624-627.
[5]	YU Lei, WANG Yunlong, CHEN Zhishen, WANG Xinchun, GAO Yugang, JIA Xiaojing. Influence of antlerbase on Notch2 gene expression and immune functionof mice with thymic lymphomas induced by ionizing radiation [J]. Journal of Jilin University Medicine Edition, 2016, 42(05): 887-891.
[6]	HU Zhihong, ZHAO Dali, XIE Zhongwei, WANG Mengying, HU Jingkun, GONG Shouliang, LIU Yang, QI Yali. Effects of pEgr1-TRAIL recombinant plasmid combined with ionizing radiation on related gene and protein expressions of death receptor pathway in breast cancer MCF-7 cells [J]. Journal of Jilin University Medicine Edition, 2016, 42(03): 419-423.
[7]	ZHANG Jing, ZHAO Dali, XIE Zhongwei, LIU Yanjun, LI Zhijun, LI Yan, GONG Shouliang, QI Yali. Effects of ionizing radiation on autophagy and apoptosis in MCF-7 cells with Beclin 1 over-and low-expressions and their regulating mechanisms [J]. Journal of Jilin University Medicine Edition, 2015, 41(06): 1139-1143.
[8]	QI Yali, ZHAO Dali, LIU Yanjun, GONG Shouliang, WANG Zhicheng. Effects of Akt combined with ionizing radiation onapoptosis, autophagy and proliferation in breast cancer MCF-7 cells [J]. Journal of Jilin University Medicine Edition, 2015, 41(01): 1-5.
[9]	FANG Fang，ZHAO Xue-lian，LI Dan-li，BAI Yang，GONG Shou-liang，LIU Yang，WANG Zhi-cheng. Effects of ionizing radiation on ROS,apoptosis and cell cycle in breast cancer stem cells [J]. Journal of Jilin University Medicine Edition, 2014, 40(06): 1132-1137.
[10]	QI Ya-li1,2, LIU Hong-bin3, XIE Zhong-wei3, LIU Yan-jun4, WANG Jian-feng2,5. Effects of ionizing radiation on proliferation and invasion of MCF-7 cells transfected with pcDNA3.1-Egr-1-AIF△1-480 plasmid [J]. Journal of Jilin University Medicine Edition, 2014, 40(05): 929-932.
[11]	ZHOU Hui,YANG Bing,TANG Quan,SUN Yuan-ming,HAN Yin,FAN Fei-yue,LIU Xiao-dong,JIA Li-li. Effect of ionizing radiation on expression of RANK in differentiation process of osteoclasts and its molecular mechanism of bone injury  [J]. Journal of Jilin University Medicine Edition, 2013, 39(6): 1127-1131.
[12]	SUN Bao-Wa, DONG Juan-Cong, WANG Jin-Hu, JIN Shun-Zi, TUN Cong-Mei. Effects of ionizing radiation on regulatory factors in different subsets of T lymphocytes of immune organs in mice [J]. J4, 2011, 37(6): 985-988.
[13]	MENG Fan-Xu, CHAN Yu-Xin, DONG Juan-Cong, JIN Shun-Zi. Effects of ionizing radiation with different doses on \|regulatory T cells and \|expression of TGF-β1 in mouse spleen  [J]. J4, 2011, 37(3): 398-402.
[14]	JI E-Chi, ZHANG Shen-Yu, WANG Hong-Yan, LI Jin-Hua, GONG Shou-Liang. Relationship between autophagy and apoptosis of MCF-7 cells induced by ionizing radiation [J]. J4, 2009, 35(6): 1007-1010.
[15]	YU Lei, LIU Yong-Zhe, SUN Shi-Long, FANG Fang, GONG Hong-Wei, CHEN Qiang, JU Gui-Zhi. Analysis on relevance between c-myc gene and thymic lymphomas of mice induced by ionizing radiation [J]. J4, 2009, 35(6): 971-974.

Effect of ionizing irradiation on expression of CD47 in bone marrow hematopoietic stem/progenitor cells in mice

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 8

References 24

Related Articles 15

Metrics

Comments

Recommended 10